Cytoarchitectonic, receptor distribution and functional connectivity analyses of the macaque frontal lobe

Based on quantitative cyto- and receptor architectonic analyses, we identified 35 prefrontal areas, including novel subdivisions of Walker’s areas 10, 9, 8B, and 46. Statistical analysis of receptor densities revealed regional differences in lateral and ventrolateral prefrontal cortex. Indeed, structural and functional organization of subdivisions encompassing areas 46 and 12 demonstrated significant differences in the interareal levels of α2 receptors. Furthermore, multivariate analysis included receptor fingerprints of previously identified 16 motor areas in the same macaque brains and revealed 5 clusters encompassing frontal lobe areas. We used the MRI datasets from the non-human primate data sharing consortium PRIME-DE to perform functional connectivity analyses using the resulting frontal maps as seed regions. In general, rostrally located frontal areas were characterized by bigger fingerprints, that is, higher receptor densities, and stronger regional interconnections. Whereas more caudal areas had smaller fingerprints, but showed a widespread connectivity pattern with distant cortical regions. Taken together, this study provides a comprehensive insight into the molecular structure underlying the functional organization of the cortex and, thus, reconcile the discrepancies between the structural and functional hierarchical organization of the primate frontal lobe. Finally, our data are publicly available via the EBRAINS and BALSA repositories for the entire scientific community.

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Materials:
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Codes used will be publicly available (lines 420-422).
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Code used for the implementation and visualization of the functional connectivity analysis will be publicly available (https://github.com/seanfw/mac aque-pfc-func-conn).
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Reporting:
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Sample-size estimation
• You should state whether an appropriate sample size was computed when the study was being designed • You should state the statistical method of sample size computation and any required assumptions • If no explicit power analysis was used, you should describe how you decided what sample (replicate) size (number) to use Since this is a neuroanatomical study without any statistical hypothesis testing, this information does not apply to this submission. We note that sample size (multimodal imaging data from four monkeys) is determent by practical and ethical constraints on non-human primate studies.

Replicates
• You should report how often each experiment was performed • You should include a definition of biological versus technical replication • The data obtained should be provided and sufficient information should be provided to indicate the number of independent biological and/or technical replicates • If you encountered any outliers, you should describe how these were handled • Criteria for exclusion/inclusion of data should be clearly stated • High-throughput sequence data should be uploaded before submission, with a private link for reviewers provided (these are available from both GEO and ArrayExpress) We used an observer-independent, quantitative method to identification of cortical borders, this method has proven to be a powerful tool in brain mapping. Detailed description can be found in the Materials and Methods section. We analyzed cyto-and receptor architecture (of 14 different receptor types), as well as the distribution of functional connectivity pattern, and various subdivisions of the prefrontal and orbital cortex were recognized consistently across all studied hemispheres, the position, extent and distribution patterns of receptors as well as cytoarchitectonic features are well comparable between individuals. Additionally, the parcellation scheme and newly defined areas were reviewed by an experienced anatomist (NPG).

Statistical reporting
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Group allocation
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